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Significance Cancer and heart disease are among the most progressive causes of mortality today. Two major regulators of these disease states are the MAP kinase and PKA signaling pathways. Ensuring… Click to show full abstract
Significance Cancer and heart disease are among the most progressive causes of mortality today. Two major regulators of these disease states are the MAP kinase and PKA signaling pathways. Ensuring proper signaling of these pathways is an essential aspect of maintaining cellular integrity and preventing disease progression. Here we identify a regulatory circuit whereby PKA phosphorylation of RKIP at S51 induces its phosphorylation by PKC, leading to up-regulation of the β-adrenergic receptor signaling and further activation of PKA. This positive feedback circuit enables rapid and robust activation of PKA in the heart and other tissues when required. This mechanism has potential applications to multiple disease states by identifying S51 as a diagnostic marker and therapeutic target.
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022
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